B Y T TRNG I HC DC H NI NGUYN MAI HNG KHO ST TNH HNHS DNG METHOTREXAT TRN BNH NHN CHA NGOI T CUNG CHA V TI BNH VIN PH SN TRUNG NG KHA LUN TT NGHIP DC S H NI - 2013 2 B Y T TRNG I HC DC H NI

NGUYN MAI HNG KHO ST TNH HNHS DNG METHOTREXAT TRN BNH NHN CHA NGOI T CUNG CHA V TI BNH VIN PH SN TRUNG NG KHA LUN TT NGHIP DC S Ngi hng dn: 1. ThS. Nguyn Th Hin 2. TS. Nguyn Thnh KhimNi thc hin: 1. B mn Y hc c s 2. Bnh vin Ph Sn Trung ng H NI - 2013 3 LI CM N Kho lun va l c hi sinh vin trnh by nhng nghin cu v vn mnhquantmtrongqutrnhhctpngthicnglmttiliuquan trnggipgingvinkimtranhgiqutrnhhctpvktquthctp ca mi sinh vin. hon thnh kho lun ny, ngoi s n lc ca bn thn, ti trn trng gi li cm n su sc n: -Ban gim hiu, Phng o to, B mn Y hc c s trng i hc Dc H Ni tn tnh ging dy ti trong sut thi hc tp va qua. y ti khng ch c truynthcho nhngkinthc nntngmcnlo cca dc s tng lai. -BanGimcvccphngbanBnhvinPhsnTrungngto mi iu kin gip cho ti thc tp v hon thnh kho lun. -c bit cho php ti gi li cm n su sc n Thc s Nguyn Th Hin Trng b mn Y hc c s Trng i hc Dc H Ni, Tin s Nguyn Thnh Khim ging vin trng i hc Y H Ni l nhng ngi dnh nhiu cng sc ch bo v hng dn ti hon thnh kho lun ny. Vi tt clng thnh knh ti xin chn thnh cm t v bit n su sc n cc gio s, ph gio s, tin s v thc s trong hi ng thng qua cng v hi ng chm kha lun tt nghip. Mt phnkhng nhchosthnhcng cakha lun nylsngvin khch l v quan tm ca nhng ngi thn, gia nh, bn b. Ti xin ghi nhn nhng tnh cm v cng lao . Xin chn thnh cm n! H Ni , ngy 19thng 5 nm 2013 Sinh vin Nguyn Mai Hng LI CAM OAN Tixincamoanbnlunvnlcngtrnhnghincukhoahc, c lpcati.Ccsliu,ktqunutronglunvnltrungthcvcngun gc r rng. TC GI KHO LUN Nguyn Mai Hng DANH MC CH VIT TT 1. BN:Bnh nhn 2. CLS :Cn lm sng 3. CNTC :Cha ngoi t cung 4. MTX :Methotrexat 5. LS:Lm sng 6. PSTW :Ph sn Trung ng 7. PSHN :Ph sn H Ni 8. PS:Ph sn 9. VTC :Vi t cung 10. hCG : Human chorionic gonadotropin 11. -hCG :Beta-human chorionic gonadotropin 12. TDKMM:Tc dng khng mong mun 13.KTKC:Kch thc khi cha 1 DANH MC BNG Bng 3.1. Phn b bnh nhn theo nhm tui ........................................................ 21 Bng 3.2. Phn b ni c tr ................................................................................. 22 Bng 3.3. Tnh trng sinh .................................................................................. 22 Bng 3.4. Cc yu t nguy c ................................................................................ 23 Bng 3.5. Nng -hCG ban u phn theo cc khong gi tr ........................... 23 Bng 3.6. Nng -hCG ban u trung bnh....................................................... 24 Bng 3.7. Kch thc khi cha ............................................................................ 24 Bng 3.8. S bin i ca nng -hCG sau liu th nht 7 ngy....................... 25 Bng 3.9. S khc bit gia t l gim nhanh v khng gim nhanh...................... 26 Bng 3.10. S bin i ca nng -hCG sau liu th hai sau 7 ngy................. 27 Bng 3.11. S bin i ca nng -hCG liu th ba sau 7 ngy........................ 29 Bng 3.12. S bin i kch thc khi cha......................................................... 29 Bng 3.13. T l thnh cng, tht bi chung .......................................................... 30 Bng 3.14. So snh t l thnh cng ...................................................................... 31 Bng 3.15. Phn tch tm yu t nguy c ca tht bi iu tr................................. 31 Bng 3.16. Phn tch tm yu t tin lng tht bi iu tr.................................... 31 Bng 3.17. Mi lin quan gia nng -hCG trc iu tr v s liu MTX....... 32 s dng thnh cng........................................................................................... 32 2 DANH MC HNH V Hnh 1.1. S di chuyn ca trng th tinh. .......................................................... 4 Hnh 1.2. Cc v tr lm t ca phi .........................................................................5 Hnh 1.3. Cng thc cu to ca Methotrexat. ....................................................... 13 3 MC LC T VN ........................................................................................................1 CHNG 1: TNG QUAN.................................................................................3 1.1. Cha ngoi t cung....................................................................................... 3 1.1.1. Cu to v sinh l vi t cung........................................................... 3 1.1.2. S di chuyn v lm t ca trng th tinh.....................................3 1.1.3. nh ngha cha ngoi t cung.......................................................... 4 1.1.4. Bin chng ca cha ngoi t cung................................................... 4 1.1.5. Phn loi ........................................................................................... 5 1.1.6. Nguyn nhn v cc yu t nguy c gy CNTC ................................ 5 1.1.6.1. Nguyn nhn.................................................................................. 5 1.1.6.2. Yu t nguy c...............................................................................6 1.1.7. Chn on thai ngoi t cung cha v...............................................7 1.1.7.1. Triu chng lm sng in hnh ..................................................... 7 1.1.7.2. Cn lm sng.................................................................................. 8 1.2. Cc phng php iu tr CNTC cha v..................................................... 9 1.2.1. Phu thut ......................................................................................... 9 1.2.2. iu tr ni khoa ............................................................................. 10 1.2.2.1. Phc n liu........................................................................... 10 1.2.2.2. Phc a liu............................................................................. 11 1.2.3. Ht khi thai di hng dn ca siu m kt hp s dng MTX... 12 1.2.4. Phng php iu tr ch cn theo di (Expectant pregnancy). ........ 12 1.3. Methotrexat ................................................................................................ 13 1.3.1. Cng thc ha hc .......................................................................... 13 1.3.2. Dc l v c ch tc dng............................................................. 13 1.3.3. Dc ng hc................................................................................ 13 1.3.4. Ch nh .......................................................................................... 14 1.3.5. Chng ch nh................................................................................ 14 1.3.6. Thn trng ...................................................................................... 15 1.3.7. Tc dng khng mong mun........................................................... 15 1.3.8. Liu dng v cch dng .................................................................. 16 1.3.9. Tng tc thuc .............................................................................. 16 4 1.3.10. Qu liu v x tr .......................................................................... 16 1.4. S dng MTX iu tr CNTC..................................................................... 16 CHNG 2:I TNG V PHNG PHP NGHIN CU................. 18 2.1. i tng nghin cu................................................................................. 18 2.2. Phng php nghin cu: ........................................................................... 18 2.3. Cc quy c nghin cu ............................................................................. 18 2.3.1. Phc MTX trn bnh nhn CNTC cha v ti bnh vin PSTW. 18 2.3.2. Quy c thnh cng........................................................................ 19 2.3.3. Quy c tht bi.............................................................................. 19 2.3.4. Quy c nh gi s bin inng -hCG................................ 20 2.4. Cch thc tin hnh v phng php thu thp thng tin.............................. 20 2.5. X l s liu............................................................................................... 20 CHNG 3:KT QU V BN LUN......................................................... 21 3.1. Kt qu....................................................................................................... 21 3.1.1. c im mu nghin cu............................................................... 21 3.1.1.1. Phn b bnh nhn theo nhm tui............................................... 21 3.1.1.2. Ni ............................................................................................ 21 3.1.1.3. Tnh trng sinh ........................................................................ 22 3.1.1.4. Yu t nguy c............................................................................. 22 3.1.1.5. Nng -hCG trc iu tr....................................................... 23 3.1.1.6. Kch thc khi cha................................................................... 24 3.1.2. Kho st hiu qu s dng MTX trn bnh nhn CNTC cha v.... 24 3.1.2.1.Khosthiu qusdngthng quasthay inng -hCG sau liu th nht........................................................................................ 25 3.1.2.2.Khosthiu qusdngthng quasthay inng -hCG sau liu th hai.......................................................................................... 27 3.1.2.3.Khosthiu qusdngthng quasthay inng -hCG sau liu th ba........................................................................................... 28 3.1.2.4.Khosthiu qus dngthng qua sbin ikchthckhi cha.......................................................................................................... 29 3.1.2.5. T l thnh cng, tht bi chung................................................... 29 5 3.1.2.6. Phn tch hi quy tm nguy c tht bi v yu t tin lng tht bi trong iu tr ............................................................................................. 31 3.1.2.7.Mi lin quan gia nng -hCG v s liu MTX s dng thnh cng.......................................................................................................... 32 3.1.2.8. Tc dng khng mong mun........................................................ 33 3.2. BN LUN............................................................................................... 33 3.2.1. c im mu nghin cu............................................................... 33 3.2.1.1. Phn b bnh nhn theo nhm tui............................................... 33 3.2.1.2. Ni ............................................................................................ 34 3.2.1.3. Tnh trng sinh ........................................................................ 34 3.2.1.4. Yu t nguy c............................................................................. 35 3.2.1.5. Nng hCG trc iu tr..................................................... 35 3.2.2. Kho st hiu qu s dng MTX trn bnh nhn CNTC cha v .... 36 3.2.2.1.Khosthiu qusdngthng quasthay inng -hCG sau liu th nht........................................................................................ 36 3.2.2.2.Khosthiu qusdngthng quasthay inng -hCG sau liu th hai.......................................................................................... 37 3.2.2.3.Khosthiu qusdngthng quasthay inng -hCG sau liu th ba........................................................................................... 38 3.2.2.4.Khosthiu qus dngthng qua sthayikchthckhi cha.......................................................................................................... 39 3.2.2.5.Khosthiuqusdngthngquatlthnhcng,thtbi chung........................................................................................................ 39 3.2.2.6. Phn tch hi quy tm yu t nguy c tht bi............................... 40 3.2.2.7. Mi lin quan gia nng -hCG v s liu MTX s dng thnh cng ............................................................................................... 40 3.2.2.8. Kho st tc dng khng mong mun sau khi tim thuc. ............ 41 KT LUN V XUT................................................................................. 42 TI LIU THAM KHO 1 T VN Cha ngoi t cung (CNTC) l mt bnh l ph khoa thng gp. CNTC c thedatnhmngnukhngcphthinviutrkpthi.Trongnhng nm gn y, t l CNTC c chiu hng tng nhanh. Anh, t l mi mc nm 2004 l 1,24% ph n mang thai, Nigeria chim 1,68%tngssinhvGhana4%tngssinh[4].TiVitNam,CNTCcxu hng tng ln tt c cc tuyn iu tr theo mt con s thng k cha y , t lgpCNTCVitNamt0,4%n0,33%tngstrnghpcthai.Theo thngk,tibnhvinTDThnhphHChMinh,tlTNTCtngt 3,073% ca sinh vo nm 2000 ln n 4,632% ca sinh nm 2005 [4],[13]. Trong cc th CNTC, CNTC v l mt cp cu s mt ca sn khoa, c th gy t vong m v con nu khng c iu tr kp thi. V vy, vic pht hin sm v iu tr CNTC cha v l vn rt cn thit. C nhiu phng php iu tr CNTC cha v. Trc y, vic iu tr ch bng phng php ngoi khoa: m, tht hocctngdntrong.NhngnmgnyiutrnikhoabngMethotrexat (MTX) dn chim u th v tnh thm mcao, phc hi sc khe nhanh v kh nng botnchc nngsinhsncho ngi ph n vitlcao.Tsaukhi c thchinlnutintrnthgiinm1982[10],nhiutcgikhcnhGary Lipscomb, Kazandi, Stovall, Ling, ch nh MTX iu tr CNTC cha v vi tlthnhcngt 81% n 96%,tlvitrngthngt 67% n 83%[9],[32]. Cn Vit Nam, cc nghin cu ca tc gi NguynVn Hc, Nguyn Th Hng, VngTinHa,NguynThKimHu,cngchothyhiuqucaMTXtrn bnhnhnCNTCchavthnhcngvitl80%n92,5%,tlvitrng thng 74% [2],[12],[6]. BnhvinPhSnTrungng(PSTW)lbnhvintuyncui,vis lng bnhnhnhngnmrtng.Bnhvinbt usdngMTXiutr ni khoa CNTC cha v t nm 2003 v cho n nay t nhiu kt qu kh quan.Phc iutrCNTCchavbngMTXthngnht,ccngnhnti y l phc n liu. 2 nngcaochtlng iu trCNTCcha v,chngtitin hnh ti Kho st tnh hnh s dng MTC trn BN CNTC cha v ti bnh vin PSTW 6 thng u nm 2012 vi mc tiu sau:. -Kho st mt s c im BN CNTC cha v c s dng MTX ti bnh vin PSTW trong 6 thng u nm 2012. -Kho st hiu qu s dng MTX theo phc n liu trn bnh nhn CNTC cha v. T araccxut gp phnnng caohiu qus dngMethotrexat trn bnh nhn CNTC cha v. 3 CHNG 1: TNG QUAN 1.1. Cha ngoi t cung 1.1.1. Cu to v sinh l vi t cung Vi t cung l ng dn trng t bung trng ti t cung, mt u m vo bng, mt u thng vi bung t cung. C 2 vi t cung, mi bn di khong 7cm n 14cm [2],[23]. Vi t cung gm 4 on: on thnh, eo, bng v phu vi [7]. on thnh nm trong thnh t cung v thng vi bung t cung qua l t cung ca vi. Eo vi l on ngn, hp, c thnh dy, gn vi sng t cung. Bng vi l on rng nht v di nht, to nn khong 2/3 chiu di ca vi. Phu vi (hay cn gi l loa vi) l on hnh phu ca vi, nm st vi bung trng. Phu vi tn cng bng nhng mm nh ngn tay gi l cc tua vi, mt trong nhng tua ny dnh vo vi trng. Vmhc,vi tcungccuto bi 3 lp:ngoicngl lpthanh mc, lp c trn gia v lp nim mc trong cng. Lp nim mc c nhiu npdc,chacctbobiumtrclngchuynvcctbotit(cvi lng),ngvaitrcungcpcht dinh dngchotrng.Lpctrngm mt tngcvngdytrongvtngcdcmngngoi.Nhngcothtnhu ngcalpcvhotngcalngchuynnimmcgipatrng c th tinh v pha t cung [7]. -Sinhlvitcung:VitcungchutcngcahormoneEstrogenv Progesteron. Estrogen lm tng s co bp tng nhu ng, tng hot ng ca t bo lng rung, progesteron lm tng tit dch v cung cp cht dinh dng cho trng thtinh.Haihormonnykthptonnsngnhungnhpnhngyphiv nui dng phi pht trin trong qu trnh ny. 1.1.2. S di chuyn v lm t ca trng th tinh Saukhithtinhthngxyra1/3ngoivitcung,trngtiptcdi chuyntrongvitcungnlmtbungtcung.Trngdichuyntrong phn cn li ca vi t cung mt 3-4 ngy [2]. 4 Non di chuyn c vo t cung l nh dch vi trng, hot ng ca t bo lngrungvitrng,tcdngginvitrngonstvitcungca progesteron [7]. Hnh 1.1. S di chuyn ca trng th tinh. 1.1.3. nh ngha cha ngoi t cung Cha ngoi t cung l trng hp trng c th tinh, lm t v pht trin ngoi bung t cung [2]. Tnsut:changoitcungchim1-2%thainghn.ylnguynnhn gytvongcaonhttrongsnkhoatrong3thng uthaik[2],[23].TiM, CNTC chim khong 2% s ph n c thai (hn 125.000 thai / nm) [23].1.1.4. Bin chng ca cha ngoi t cung Vi t cung (VTC) khng m bo cho thai lm t, v nim mc ca VTC t bin i so vi nim mc t cung v lp c VTC rt mng do thai ch pht trin c mt thi gian ngn ri nhng bin chng s xy ra. l: - V VTC: do gai rau n su vo lp c lm thng VTC, hoc do VTC cng to lm v vi, ng thi cc nhnh mch mu cng b v gy chy mu vo bng, mc chy mu c th khc nhau, c th gy t vong. - Sy thai: v thai lm t lc ch nn d b bong ra gy sy v chy mu [2]. 5 1.1.5. Phn loi Thaingoitcungcthlvitcung,bungtrnghoctrongbng, trong ng c t cung. Thai bung trng v trong bng rt him gp. Hnh 1.2. Cc v tr lm t ca phi 1.1.6. Nguyn nhn v cc yu t nguy c gy CNTC 1.1.6.1. Nguyn nhn Nguyn nhn (NN) gy CNTC chia lm 2 loi chnh: NN c hc v NN c nng. * Nguyn nhn c hc:-Tnthngvitcungdovim nhim:vimvitcunggyhintng dnh lm gim s lng lng mao ca t bo lm cho thnh vi t cung dy, cng, gimnhung,gimslngcctbohnhtr, lmhplngVTC.Gytc hontonhaykhnghontonvitcung,cuicngdnnchangoit cung.VimdnhquanhVTCdonhimkhunsau,sausythai,vimrut tha, lc ni mc t cunglm vi trng bin dng. Mt hoc gim cc t bo c on k2% Vi trng (on eo) 12% bng him gp Vi trng (on bng) 78% C t cung 0.5-1% Bung trng 0.7-1% on loa vi 5% 6 lngvtbochtit,cng nhlungdchtronglngvitcungclilm chmqutrnhvnchuyncatrnggyCNTC.Tinsvim nhimphnph lm tng thai ngoi t cung ln gp 46 ln [16]. - Khi u vi t cung: Cc khi u vi t cung chn p hoc pht trin vo lngVTCgyhplngvit cung.Trongqutrnhtrngdichuynv bung t cung gp phi ch tc v lm t ti gy CNTC. - S bt thng ca vi t cung: Do cu trc gii phu ca vi t cung khng hon chnh, d dng VTC hoc VTC b co tht bt thng gy CNTC [2].* Nguyn nhn c nng: -Trng ivng:Nonphngrat bungtrngbnnynhngli ivng qua vi t cung bn i din gy CNTC. -Rilon cn bng nitit:nh hngtis co bpcavit cung hoc lm gim s chuyn ng ca t bo lng mao trong lng vi t cung nh hng ti s di chuyn ca phi ti bung t cung gy CNTC. -Dobnthnphi:Phiphttrinqunhanhvtohntronglngvi t cung, do phi c th khng di chuyn c gy CNTC. 1.1.6.2. Yu t nguy c T cc nguyn nhn CNTC nu ra trn, ta c ccyu t nguy c dn n CNTC. Ngoiyu t vim nhim, vim dnh quanh vi t cung v khi u, vn cn rt nhiu cc yu t nguy c khc: -Vimnhimngsinhdclungy:lmthayiqutrnhchuynha ca cc t bo nim mc VTC, lm thng tn b phn cm th ca t cung i vi vic ht trng lm t [2].- Nhim Chlamydia: nguy c ny c th gii thch c bng gy nn s gia tngcaththprokineticin2(PROKR2)tivitrng.Sthayitnhiuca PROKR2cthtoramtmitrngthunlichoslmtcaphi,nhim 7 trngchlamydiaclinquancnghathngkvinnggiatngca PROKR2 vi trng, t d a n nguy c lm t ngoi t cung [26]. - No ht thai: nguy c CNTC ca nhng ph n c tin cn no ht thai l t2-5ln[4],[14].asccgithuytchorngvicnohtthaiantnh trngvimnhimnimctcungvngdntrng,lmnhhngnsdi chuyn ca phi vo bung t cung dn n CNTC.- Thuc trnh thai: khi s dng vin trnh thai n thun cha progestin liu thp, vn cn mt t l nht nh nguy c gy CNTC [5],[23]. -TinsCNTCvtinsphuthutvitcung:Ccphnctins CNTC c kh nng ti pht CNTC gp 46 ln so vi ph n bnh thng. Nguyn nhn l do cc yu t ny trong qu kh gy ra nhng tn thng vi t cung, t gy CNTC [16]. - Sinh sn h tr: Cc phng php sinh sn h tr lm tng t l CNTC nh ccbinphpthtinhtrongngnghim,chuynphiquavitcung,haykch rng trng bng Gonadotropin [2],[23] . -tdngctcung(DCTC):Nguynnhncthgiithchdovim nhim ti ch khi xut hin vt l trong bung t cung. Tuy nhin, ch c tin cn s dng DCTC v nga thai bng DCTC tht bi c lin quan vi CNTC [16]. Tngqut,vicnhgiccyu tnguycgyCNTCcnghartln bi n gp phn cnh gic, cnh bo nhm hn ch CNTC.1.1.7. Chn on thai ngoi t cung cha v 1.1.7.1. Triu chng lm sng in hnh - Triu chng c nng: tam chng in hnh +Ttkinh:hayckhichchmkinhvingyhoccrilonkinh nguyt, c th c du hiu nghn, v cng. + au bng: vng h v, mt bn, m . 8 + Huyt ra t mt, r r, mu nu en, c khi ln mng, khng ng. - Triu chng thc th + Bng cng nh hoc hi cng. + C t cung hi tm, mm, ng kn, c mu en t trong lng t cung. + T cung ln hn bnh thng, mm, khng tng xng vi tui thai. +Ckhiucnhtcungmm,bkhngr,ding,chmau hoc him hn c th s thy khi u c dng hi di theo chiu di ca vi t cung [2],[5]. 1.1.7.2. Cn lm sng -Sium:khngctithaitrongbungtcung,ckhimvanghnhp hoc c hnh nh ti thai ngoi t cung. C th c hnh nh t dch cng sau, hoc trong bng. Nu siu m ng bng nghi ng phi siu m ng m o kim tra [2]. - Ni soi bng: y l phng php gip xc nh chn on v x tr. Qua soi bng gip quan st ng dn trng d dng, tuy nhin nu thai qu nh cng c th sai st khong 3-4%. - Xt nghim: nh lng -hCG l xt nghim sng lc gip pht hin sm CNTC v theo diiutrCNTC.BnchthCGlmtGlycoproteinccutrcginghormon Glycoprotein ca tuyn yn. Phn t cu to gm 2 chui v , hai chui ny lin ktvinhau bilinktkhng ng hatr, kncvtnh in.Chui ging chui ca cc hormon LH, FSH v TSH. Chui ging chui ca LH 80%, ch khclcthm on peptittncnggm 24 acidamin.on peptittncng ny quyt nh tnh c hiu ca hCG nn nh lng -hCG chnh xc hn nhiu so vi hCG.nhlngnng-hCGbngphngphpmindchmenvinhy 25mUI/ml l phng php ph bin nht hin nay. i vi thai bnh thng, -hCG 9 tng rt nhanh sau khi th tinh 8 ngy v s tng ln gp i c sau 48h-72h. Nu khng tng c nh vy v siu m khng thy thai trong t cung th nn nghi ng thai ngoi t cung [2],[23]. CLS nng -hCG khng phi lyu t mu cht trong chn on CNTC song li l yu t quyt nh trong la chn phng php iu tr v kt qu iu tr. Vi khong nng -hCG ban u